The effect of rutin, a flavonoid present in onions, apples, tea and red wine, on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) was analyzed using in vitro as well as in vivo systems. The level of nitrite in lipopolysaccharide (LPS) stimulated BALB/c mice (88.21 microM) was significantly reduced in rutin treated animals (16.92 microM). The nitrite level in concanavalin-A (Con-A) treated control animals (77.15 microM) was also significantly reduced to 11.03 microM when the animals were pretreated with rutin. The drastically elevated levels of TNF-alpha in LPS stimulated animals (686.8 pg/ml) was lowered by pretreatment with rutin (182.4 pg/ml). Rutin also inhibited Con-A induced TNF-alpha production. Rutin inhibited nitrite production by activated macrophages in vitro (74.75 microM) to the normal level (16.13 microM) at a concentration of 5 microg/ml. In vitro L929 bioassay also showed inhibition of TNF-alpha production by rutin treatment.